Molecular characterization of MPS IIIA, MPS IIIB and MPS IIIC in Tunisian patients

• Published in: Clinica chimica acta 2011-11, Vol.412 (23-24), p.2326-2331
• Main Authors: Ouesleti, S., Brunel, V., Turkia, H. Ben, Dranguet, H., Miled, A., Miladi, N., Dridi, M.F. Ben, Lavoinne, A., Saugier-Veber, P., Bekri, S.
• Format: Article
• Language: English
• Subjects: Child, Preschool; Humans; Large-scale deletion; Mucopolysaccharidoses - classification; Mucopolysaccharidoses - genetics; Mutation; Polymerase Chain Reaction; QMPSF; Sanfilippo disease; Tunisia
• ISSN: 0009-8981; 1873-3492
• DOI: 10.1016/j.cca.2011.08.032

Sanfilippo syndrome (mucopolysaccharidosis type III, MPS III) is a progressive disorder in which patients are characterized by severe central nervous system degeneration together with mild somatic disease. MPS III results from a deficiency in one of the four enzymes involved in the heparan sulfate degradation, with sulfamidase (SGSH), α-N-acetylglucosaminidase (NAGLU), acetyl-coenzyme A: α-glucosaminide N-acetyltransferase (HGSNAT), and N-acetylglucosamine-6-sulfatase (GNS) being deficient respectively in MPS IIIA, MPS IIIB, MPS IIIC and MPS IIID. Mutation screening using PCR reaction/sequencing analysis on genomic DNA fragments was performed in seven Tunisian index cases with MPS IIIA, three with MPS IIIB and two with MPS IIIC. QMPSF (Quantitative Multiplex PCR of Short fluorescent Fragments) analysis was developed for the detection of genomic deletions and duplications in the SGSH gene. These approaches allowed the identification of 11 mutations, 8 of them were novel including a mutation involving the start codon (p.Met1?), one small duplication (p.Leu11AlafsX22), one small deletion (p.Val361SerfsX52) and a large deletion of exon 1 to exon 5 in the SGSH gene, one missense mutation (p.Pro604Leu) and one nonsense mutation (p.Tyr558X) in the NAGLU gene and, finally, one missense mutation (p.Trp627Cys) and one nonsense mutation (p.Trp403X) in the HGSNAT gene. ►First study on molecular defect in Tunisian MPSIII patients. ►Molecular characterization and clinical finding in 13 patients from 12 families. ►Description of 11 different mutations of which 8 are reported here for the first time. ►Large-scale deletion of 7093bp (SGSH exons 1–5, SLC26A11 exon 1-part of the exon 2).